The Italy forward is one of three players who may struggle to feature, with centre-back Vlad Chiriches and holding midfielder Amadou Diawara also sidelined with injury.
Insigne strained a muscle in his right leg during the warm-up ahead of Thursday's defeat to Red Bull Salzburg, and is expected to take at least three weeks to recover.
Chiriches, meanwhile, suffered a hamstring injury late on in Austria and has been given the same timeframe for recovery.
Diawara has a fracture in his right foot and will also be assessed in three weeks' time, but is the least likely to feature.
Of the three, only club captain Insigne is a guaranteed starter, pairing Belgium forward Dries Mertens or Polish striker Arkadiusz Milik in attack, while Chiriches is firmly behind first-choice pairing Kalidou Koulibaly and Nikola Maksimovic in the centre-back pecking order, with Raul Albiol also ahead of him, albeit sidelined with injury himself.
Diawara, 21, is an option in midfield alongside Allan, but Fabian Ruiz was most likely to get the nod.
The news will be welcome for Arsenal fans, who may have feared the thought of Insigne wreaking havoc on the right-hand side of their defence, particularly with first-choice right-back Hector Bellerin a long-term absentee, alongside Rob Holding and Danny Welbeck.
Napoli arguably represented the toughest possible draw for the Gunners, and playing one leg against a side without their captain and second top scorer across all competitions will certainly come as a boost to Unai Emery's camp.
The Gunners, while sitting fourth in the Premier League, face a fierce fight for their top-four spot, and winning the Europa League would guarantee a Champions League place ahead of next season.
They recovered from a 3-1 deficit in France to progress 4-3 on aggregate against Rennes after a 3-0 win at the Emirates Stadium, with a Pierre-Emerick Aubameyang brace and an Ainsley Maitland-Niles header sending them through.
Napoli, meanwhile, survived a 3-1 second-leg defeat to Salzburg after an impressive 3-0 win in the first leg game them enough of a cushion in order to progress.